The studies proposed in the application seek to gain further understanding of the cardiotoxicity of digitalis. We have tried to gain further understanding of basic mechanisms involved in the toxic arrhythmogenic properties of the cardiac glycosides. One initial objective was to pursue early evidence that areas in the brain stem may be the locus for the neurofacilitory effects of digitalis in inducing cardiac arrhythmias. A second objective was to study if differences in the sensitivity of Purkinje fibers and working myocardium to the effects of digitalis existed. Both areas of study have provided fruitful avenues of investigation and I believe we are able in part to further understand the reasons and mechanisms for the toxic effect of digitalis.